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Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

Ruan S BastosChristiane P O de AguiarJorddy Nevez CruzRyan da Silva RamosNjogu M KimaniJoão S N de SouzaMariana H ChavesHumberto Fonseca de FreitasSamuel Silva da Rocha PitaCleydson Breno Rodrigues Dos Santos
Published in: International journal of molecular sciences (2024)
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 M pro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for M pro , ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and M pro , with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with M pro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
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